Changes in gene expression in somatic cells of rat testes resulting from hormonal modulation and radiation-induced germ cell depletion.

Changes in gene expression in somatic cells of rat testes resulting from hormonal modulation and radiation-induced germ cell depletion.
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激素调节和辐射诱导的生殖细胞耗竭导致大鼠睾丸体细胞基因表达的变化。

DOI:
10.1095/biolreprod.109.078048
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发表时间:
2010
影响因子:
3.6
通讯作者:
Meistrich,MarvinL
Meistrich,MarvinL
中科院分区:
生物学2区
文献类型:
--
作者:
Zhou,Wei;Bolden-Tiller,OlgaU;Shetty,Gunapala;Shao,ShanH;Weng,ConnieC;Pakarinen,Pirjo;Liu,Zhilin;Stivers,DavidN;Meistrich,MarvinL

文献摘要

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虽然促性腺激素和雄激素是正常精子发生所必需的,睾酮和卵泡刺激素(FSH)是抑制受辐射大鼠精原细胞分化的原因,但很难确定所涉及的特定基因。为了研究可能参与这些过程的睾丸体细胞基因表达的特异性睾丸调节变化,而不需要改变生殖细胞群体的并发症,我们使用了辐照过的LBNF-1大鼠,其睾丸除了少数A型精原细胞外几乎只含有体细胞。三个不同的组,这些大鼠进行了治疗与各种组合的促性腺激素释放激素拮抗剂,雄激素受体拮抗剂(氟替卡松),睾酮和FSH,我们比较了基因表达水平2周后,那些只照射大鼠的微阵列分析。通过将基因表达模式分为3种主要模式和11种亚模式,我们在一项研究中成功地区分了睾丸激素、促黄体生成素(LH)和FSH特异性调控的基因与睾丸中大量非睾丸激素调控的基因。我们发现,激素产生更显着的基因表达上调比下调:Tehran有最强的上调作用,LH有一个温和的,但明显的上调作用,FSH有一个轻微的上调作用。我们还分别确定了体细胞基因,长期上调辐射。因此,本研究确定了基因表达的变化,可能是负责激素作用于体细胞,以支持正常的精子发生和照射后精原细胞发育中的精子介导的阻滞。
Although gonadotropins and androgen are required for normal spermatogenesis and both testosterone and follicle-stimulating hormone (FSH) are responsible for the inhibition of spermatogonial differentiation that occurs in irradiated rats, it has been difficult to identify the specific genes involved. To study specific hormonally regulated changes in somatic cell gene expression in the testis that may be involved in these processes, without the complication of changing populations of germ cells, we used irradiated LBNF1rats, the testes of which contain almost exclusively somatic cells except for a few type A spermatogonia. Three different groups of these rats were treated with various combinations of gonadotropin-releasing hormone antagonist, an androgen receptor antagonist (flutamide), testosterone, and FSH, and we compared the gene expression levels 2 wk later to those of irradiated-only rats by microarray analysis. By dividing the gene expression patterns into three major patterns and 11 subpatterns, we successfully distinguished, in a single study, the genes that were specifically regulated by testosterone, by luteinizing hormone (LH), and by FSH from the large number of genes that were not hormonally regulated in the testis. We found that hormones produced more dramatic upregulation than downregulation of gene expression: Testosterone had the strongest upregulatory effect, LH had a modest but appreciable upregulatory effect, and FSH had a minor upregulatory effect. We also separately identified the somatic cell genes that were chronically upregulated by irradiation. Thus, the present study identified gene expression changes that may be responsible for hormonal action on somatic cells to support normal spermatogenesis and the hormone-mediated block in spermatogonial development after irradiation.